Orbitofrontal cortex, decision-making and drug addiction

Abstract

The orbitofrontal cortex, as a part of prefrontal cortex, is implicated in executive function. However, within this broad region, the orbitofrontal cortex is distinguished by its unique pattern of connections with crucial subcortical associative learning nodes, such as basolateral amygdala and nucleus accumbens. By virtue of these connections, the orbitofrontal cortex is uniquely positioned to use associative information to project into the future, and to use the value of perceived or expected outcomes to guide decisions. This review will discuss recent evidence that supports this proposal and will examine evidence that loss of this signal, as the result of drug-induced changes in these brain circuits, might account for the maladaptive decision-making that characterizes drug addiction.

Figure I

Anatomical relationships of the OFC (blue) in rats and monkeys. Based on their pattern of connectivity with the mediodorsal thalamus (MD, green), amygdala (orange) and striatum (pink), the orbital and agranular insular areas in rat prefrontal cortex are homologous to the primate OFC. In both species, the OFC receives robust input from sensory cortices and associative information from the amygdala, and sends outputs to the motor system through the striatum. Each box illustrates a representational coronal section. Additional abbreviations: AId, dorsal agranular insula; AIv, ventral agranular insula; c, central; CD, caudate; LO, lateral orbital; m, medial; NAc, nucleus accumbens core; rABL, rostral basolateral amygdala; VO, ventral orbital, including ventrolateral and ventromedial orbital regions; VP, ventral pallidum.

Figure I

Neural activity in the OFC in anticipation of trial events. Neurons in the rat OFC were recorded during performance of an eight-odor, Go–NoGo odor-discrimination task. The activity in four different orbitofrontal neurons is shown, synchronized to four different task events (a–d). Activity is displayed in raster format at the top and as a peri-event time histogram at the bottom of each panel; labels over each figure indicate the synchronizing event and any events that occurred before or after light onset (LT-ON), odor poke (OD-POK), odor onset (OD-ON), water poke (WAT-POK) or water delivery (WAT-DEL). Numbers indicate number of trials (n) and number of spikes per second. The four neurons each fired in association with a different event, and the firing in each neuron increased in anticipation of that event. Adapted, with permission, from [87].

Figure 1

Signaling of outcome expectancies in the orbitofrontal cortex. Black bars show the response on trials involving the preferred outcome of the neurons in the post-criterion phase. White bars show the response to the non-preferred outcome. Activity is synchronized to odor onset and displayed in 100 ms bins; red boxes indicate the average duration of odor sampling and of the delay between responding and reinforcement when a response was made at the fluid well. (a) The average response of neurons that responded selectively during a delay period early in learning, after the rat went to the fluid well but before delivery of one of the outcomes (Pre). This activity signals the expected outcome after responding. (b) Later (Post), these neurons became activated by the odor cue that predicted the preferred outcomes of the neurons after learning, thereby signaling the expected outcome at the time the decision to respond is made. (c) This pattern switched after reversal of the odor–outcome associations (Rev). Average firing rate is shown on the y-axis in spikes per second. Adapted, with permission, from [13].

Figure 2

Effects of neurotoxic lesions of the orbitofrontal cortex (OFC) on performance in a reinforcer devaluation task. (a) Control rats and rats with bilateral neurotoxic lesions of the OFC were trained to associate a conditioned stimulus (CS, light) with an unconditioned stimulus (US, food). Over four sessions, both lesioned and control rats developed a conditioned responding at the food cup during light presentation. This food-cup response is represented as the percentage of total behavior. The lesion had no effect on the development of the food-cup response. (b) The rats then received presentations of the food item in their home cages followed by illness induced by lithium chloride (LiCl) injection. Some rats in each group received paired presentations of food and illness (black circles and squares); others received unpaired presentations (white circles and squares). Rats that received paired presentations stopped consuming the food item (i.e. the food stimulus was ‘devalued’). Again, no effect of lesion was observed. (c) The following day, the rats were returned to the training environment, and conditioned responses to the light cue were measured. When exposed to the light CS, control rats that had received paired presentations of food and illness (for which the food had been devalued; white bars on the left) showed reduced conditioned responses to the food cup compared with unpaired controls (white bars on the right; asterisk indicates P<0.05). Rats with OFC lesions did not show this decrease in conditioned response as a result of reinforcer devaluation. Lower panels adapted, with permission, from [23] © (1999) the Society for Neuroscience.

Figure 3

Effects of cocaine treatment on performance in the reinforcer devaluation task (Figure 2). Saline- and cocaine-treated rats were trained to associate a conditioned stimulus (CS, light) with an unconditioned stimulus (US, food). (a) Over four session blocks, both cocaine- and saline-treated rats developed a conditioned responding at the food cup during light presentation. This food-cup response is represented as the percentage of total behavior. There was no effect of the lesion on the development of the food-cup response. (b) The rats then received presentations of the food item in their home cages followed by illness induced by LiCl injection. Some rats in each group received paired presentations of food and illness (black circles and squares) while others received unpaired presentations (white circles and squares). Rats that received paired presentations stopped consuming the food item, both in their home cage and in the testing chamber (‘Box’). Again, no effect of lesion was observed. (c) The following day, the rats were returned to the training environment, and conditioned responses to the light cue were measured. Control rats that had received paired presentations of food and illness showed reduced conditioned responses to the food cup compared with unpaired controls. Rats with orbitofrontal lesions did not show this decrease in conditioned response as a result of reinforcer devaluation. This effect was observed while all four groups showed normal extinction of responding during the probe test (inset). Adapted, with permission of Oxford University Press, from [24].